During this period, a sensitive, specific and robust method to simultaneously determine enantiomeric SAL and its precursor DA in biological samples using simple chemical derivatization and chiral separation coupled with electrospray ionization-tandem mass spectrometry (ESI-MS/MS). A linear response was observed for each enantiomer over the 0.5-500pg range, with correlation coefficients >0.999. The limit of quantitation assayed in the plasma matrix was below 10pg for each SAL enantiomer and 100pg for DA. Both coefficient of variance and error for inter- and intra-day measurements in the blank plasma were less than 10% for SAL and DA in the concentration range of 10-4,000pg/mL and 0.1-8ng/mL, respectively, indicating that precision and accuracy were acceptable for reliable determination of biological fluids. This strategy enabled routine determination of SAL enantiomers and DA from 0.5mL human plasma and cerebrospinal fluids, ten fold less volume than that required by the existing methodology. This assay method is currently applied to investigate the effect of alcohol on SAL levels and their enantiomeric distribution in human plasma and CSF. The correlations between plasma and CSF levels were found with both (S)-SAL and (R)-SAL but not with DA. To examine the effects of diet on the plasma SAL level, rats were fed with SAL by gavage. Preliminary data indicated that plasma SAL levels were strongly influenced by the SAL ingestion. The influence of diet and alcohol on SAL levels in human plasma and CSF is currently under investigation.